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Activity of reverse transcriptase inhibitors in monocyte-derived dendritic cells: a possible in vitro model for postexposure prophylaxis of sexual HIV transmission

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dc.contributor.author Van Herrewege, Y. en_US
dc.contributor.author Penne, L. en_US
dc.contributor.author Vereecken, C. en_US
dc.contributor.author Fransen, K. en_US
dc.contributor.author van der Groen, G. en_US
dc.contributor.author Kestens, L. en_US
dc.contributor.author Balzarini, J. en_US
dc.contributor.author Vanham, G. en_US
dc.date.accessioned 2007-12-06T14:48:46Z
dc.date.available 2007-12-06T14:48:46Z
dc.date.issued 2002 en_US
dc.identifier.issn 0889-2229 en_US
dc.identifier.doi http://dx.doi.org/10.1089/088922202320567833
dc.identifier.other ITG-M1A en_US
dc.identifier.other ITG-M2B en_US
dc.identifier.other ITG-M3B en_US
dc.identifier.other ITG-M4A en_US
dc.identifier.other ITG-M5A en_US
dc.identifier.other ITG-M6A en_US
dc.identifier.other ITG-MLA en_US
dc.identifier.other MICRO en_US
dc.identifier.other U-IMMUN en_US
dc.identifier.other U-VIROL en_US
dc.identifier.other JIF en_US
dc.identifier.other DOI en_US
dc.identifier.other ABSTRACT en_US
dc.identifier.other FTA
dc.identifier.uri http://hdl.handle.net/10390/2046
dc.description.abstract Because prevention of heterosexual HIV transmission is not always possible, it is important to develop effective strategies of postexposure prophylaxis (PEP). Since in vivo comparison of drug potency is difficult, we developed an in vitro model with cells resembling primary targets during sexual transmission: monocyte-derived dendritic cells (MO-DCs), Langerhans cells (MO-LCs), and resting autologous CD4(+) T cells. Nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs, respectively) were evaluated for their antiviral activity, when added immediately after infection or at a later time point. In parallel, their immune-suppressive effect was examined by measuring inhibition of mixed MO-DC/allogeneic CD4(+) T cell cultures. Most RTIs potently inhibited HIV replication, even if added 24 hr after infection (representing PEP). The sensitivity to antiretroviral drugs was similar in HIV-infected MO-DCs and MO-LCs, but decreased in cocultures with resting autologous CD4(+) T cells. The NNRTIs efavirenz and UC-781 as well as the NRTIs AZT, 3TC, and d4T showed a similar high potency in MO-DC plus autologous CD4(+) T cell cocultures as compared with CEM T cells, whereas their activity in phytohemagglutinin/interleukin 2 (PHA/IL-2)-activated CD4(+) T cells was lower. The dideoxynucleoside RTI abacavir as well as the phosphonates (R)-PMPA and PMEA were more active in infected MO-DCs as compared with either CEM T cells or PHA/IL-2 activated CD4(+) T cells. Infection in cocultures of MO-DCs and autologous CD4(+) T cells could be aborted in a proportion of the cultures, with high concentrations of PMEA and/or efavirenz, but not with AZT. Suppressive activity in mixed leukocyte cultures was observed only at very high concentrations of RTI. Our data suggest that cocultures of MO-DCs and autologous CD4(+) T cells can be used as a possible in vitro model to explore protocols for PEP after sexual HIV transmission. en_US
dc.language English en_US
dc.subject Viral diseases en_US
dc.subject HIV en_US
dc.subject AIDS en_US
dc.subject Chemoprophylaxis en_US
dc.subject Post-exposure en_US
dc.subject Drug development en_US
dc.subject Reverse transcriptase inhibitors en_US
dc.subject Dendritic cells en_US
dc.subject Monocytes en_US
dc.title Activity of reverse transcriptase inhibitors in monocyte-derived dendritic cells: a possible in vitro model for postexposure prophylaxis of sexual HIV transmission en_US
dc.type Article en_US
dc.citation.issue 15 en_US
dc.citation.jtitle AIDS Research and Human Retroviruses en_US
dc.citation.volume 18 en_US
dc.citation.pages 1091-1102 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/12396448
dc.citation.jabbreviation AIDS Res Hum Retroviruses en_US


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